A novel frameshift deletion in PLS3 causing severe primary osteoporosis

Area of Science:

• Genetics
• Molecular Biology
• Orthopedics

Background:

• Mutations in the plastin-3 (PLS3) gene are linked to severe primary osteoporosis.
• PLS3, located on the X chromosome, typically affects males more severely.
• The precise molecular function of plastin-3 remains under investigation.

Observation:

• A case study of an 8-year-old Greek boy with severe primary osteoporosis, multiple fractures, and symptoms resembling osteogenesis imperfecta is presented.
• Clinical features included blue sclerae, joint hypermobility, low bone mineral density, kyphosis, hearing loss, and mild dysmorphic features.
• Genetic testing excluded mutations in COL1A1 and COL1A2, common genes for osteogenesis imperfecta.

Findings:

• Sanger sequencing identified a novel de novo frameshift deletion (NM_005032: c.1096_1100delAACTT, p.(Asn366Serfs*5)) in exon 10 of the PLS3 gene.
• This genetic finding confirmed the diagnosis of PLS3-related osteoporosis.
• This represents a new mutation associated with this rare genetic bone disorder.

Implications:

• The findings underscore the significant clinical overlap between type I collagen disorders and PLS3-related skeletal fragility.
• This case highlights the critical importance of screening the PLS3 gene in pediatric patients presenting with multiple fractures and low bone mineral density.
• Early and accurate genetic diagnosis of PLS3 osteoporosis is essential for appropriate genetic counseling and management.